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Three Part Question

Is [dexmedetomidine] a [safe and effective sedation medication] in [children and adolescents requiring sedation for painful procedures in the Emergency Department]?

Clinical Scenario

An 8 year old girl is brought to your emergency department after falling in the local park and sustaining a laceration across her cheek. The wound needs to be cleaned and sutured. You feel that she will require sedation in order to fully comply during the procedure, and have heard about dexmedetomidine which is already being used safely and effectively in sedation for painless procedures. You wonder if this agent will provide you with effective procedural sedation without increasing her adverse event risk.

Search Strategy

Medline using the OVID interface and Embase
(((children).ti,ab OR (child).ti,ab OR (pediatric).ti,ab OR (paediatric).ti,ab OR (pediatr* OR paediatr*).ti,ab OR CHILD/OR PEDIATRICS/) AND ((dexmedetomidine).ti,ab OR (precedex).ti,ab OR DEXMEDETOMIDINE/)) [DT 1997-2017] [Human age groups Infant, newborn Or Infant OR child, preschool OR Child OR Adolescent Or Young adult]. Limited to English.

Search Outcome

440 papers found of which 337 irrelevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Canpolat 2012 Turkey	60 children aged between 8 and 60 months with second degree burns ranging from 5-25% total body surface area undergoing dressing change were randomised to one of two groups: ketamine/propofol (KP) combination for induction with propofol boluses as required or ketamine/dexmedetomidine (KD) combination on induction with dexmedetomidine boluses as required.	Prospective, randomised, open controlled study (level 2 evidence)	Ramsay Sedation Score	No statistical significance in sedation scale quoted in text but actual scores and analysis not described	1. Introduction of bias as the anaesthetist was not blinded to the two groups and also single-handedly administered all the sedation and performed all the monitoring 2. Dexmedetomidine was not the sole agent
			Desaturation <90% and respiratory depression	4 patients in KP group experienced respiratory depression and desaturation <90% (13.3%) but none in KD group (p=0.04)
			Changes in heart rate	No statistically significant episodes of tachycardia or bradycardia in either group
			Blood pressure	Systolic values in group KD showed a significant increase after induction (P < .05) No significant change in diastolic pressure in either group
			Surgeon satisfaction (blinded to sedation drug)	No significant difference in surgeon satisfaction between groups (p=0.166)
			Recovery time	Longer recovery time in KD group (36.6 min) compared to KP group (27.7 min) (p=0.01)
Singh 2014 India	112 children, ASA I, aged 3 to 10 years undergoing invasive dental procedures (root canal or tooth extraction) were divided into one of four groups: K (ketamine 8mg/kg), D1 (dexmedetomidine 3µg/kg), D2 (D dexmedetomidine 4µg/kg) and D3 (dexmedetomidine 5µg/kg). The drugs were all given orally.	Prospective, triple blind, randomised, controlled study (level 2 evidence)	Onset of sedation	Significantly more rapid onset with K (21.1 min) and D3 (23.6 min) compared to D1 (42.0 min) and D2 (35.6 min) (p<0.001)	Sedation and amnesia scales modified from other guidelines but no validation work undertaken
			Recovery from sedation	Significantly longer recovery with K (103.3 min) and D3 (108.6 min) compared to D1 (79.4 min) and D2 (90.4 min) (p<0.001)
			Analgesia (measured by FLACC scale)	Better analgesia with K and D3 with significantly lower intra-and post-operative scores compared to D1 and D2 (p<0.001)
			Level of sedation	D3 provided ‘adequate’ sedation in highest number of sessions (82.1%) but difference was not statistically significant (p=0.433)
			Amnesia	Significantly higher in K compared D1, D2 and D3 (p<0.01)
			Adverse events	Adverse events (vomiting and hallucinations) were significantly higher in group K (in 25% of the sessions) compared to D groups
			Changes in physiological parameters	K resulted in significantly higher heart rates (104.6 bpm) compared to D1, D2 and D3 (98.5, 98.8 and 94.2 bpm respectively) (p<0.001) and significantly higher systolic blood pressure (116.1 mmHg) compared to D1, D2 and D3 (111.4, 110.7 and 109.5 mmHg respectively) (p<0.001). No significant difference in oxygen saturations, diastolic blood pressure or respiratory rate between the four groups
			‘Overall success’: physiological parameters remaining within 20% of baseline; oxygen saturations ? 95%; adequate depth of sedation; use of restraint not required; absence of adverse events	Proportionately higher ‘overall success’ in D3 (78.6%) followed by D2 (75%), D1 (57.1%) and K (53.6%). However, difference did not reach statistical significance on chi-square testing (p=0.235)
Jewett 2009 USA	Two patients with anterior shoulder dislocations: 1. 18yr female (80 kg) given dexmedetomidine 120µg titrated intravenously over 2 minutes. 2. 19yr female (60 kg) given dexmedetomidine 75µg, titrated intravenously over 3 minutes.	Case report (level 4 evidence)	Onset of sedation	4 minutes and 5 minutes respectively	Case report of only 2 patients
			Change in physiological parameters	No change in respiratory rate or blood pressure in either case. Both cases had transient drops in heart rate to 75 bpm and 45 bpm respectively
			Successful reduction of dislocation	Yes
			Pain	None
			Recall	None

Comment(s)

Dexmedetomidine is a selective ?-2 agonist used for sedation for critically ill patients in intensive care and in children to facilitate painless procedures. It does not cause respiratory depression but can cause a drop in heart rate and blood pressure via its suppressive effects on sympathetic nervous system activity. Although its analgesic properties are well documented, only three studies have described the use of dexmedetomidine in procedural sedation for painful procedures in children and adolescents. A prospective, triple blind, randomised controlled study by Singh et al (2014) demonstrated that oral dexmedetomidine at 5 µg/kg can be safely and successfully used for invasive painful procedures with analgesic and sedative effects equivalent to oral ketamine but with the advantage of causing significantly fewer adverse effects such as vomiting and emergence phenomena. Two case reports by Jewett and Phillips (2010) demonstrated that intravenous dexmedetomidine 1.25 µg/kg – 1.5 µg/kg boluses provided rapid, effective and safe sedation for dislocation shoulder reduction in adolescents. Intravenous dexmedetomidine is typically used as an infusion; Jewett and Phillips’ experience with bolus therapy suggests dexmedetomidine could have useful applications for short, urgent painful procedures and may offer a particular advantage in cases where respiratory depression would be problematic (such as children and adolescents with a difficult airway or aspiration risk) or in cases where hypertension or tachycardia would be deleterious. Finally, an open-label prospective, randomised controlled study by Canpolate et al (2012) demonstrated that dexmedetomidine in combination with ketamine provides effective sedation and analgesia for skin graft dressing changes in children without adverse effects, with significantly lower rates of respiratory depression when compared to propofol-ketamine combination.

Clinical Bottom Line

Dexmedetomidine shows promise as a safe, effective agent for paediatric procedural sedation for painful procedures but due to lack of good quality studies at present its use cannot be recommended. Further well-designed randomised controlled trials are required.

References

1. Canpolat DG, Esmaoglu A, Tosun Z et al. Ketamine-Propofol vs Ketamine-Dexmedetomidine combinations in paediatric patients undergoing burn dressing changes. Journal of Burn Care Research 2012;33:718-722.
2. Singh C, Pandey RK, Saksena AK et al. A comparative evaluation of anglo-sedative effects of oral dexmedetomidine and ketamine: a triple blind, randomised study. Paediatric Anaesthesia 24 (2014) 1252-1
3. Jewett J and Phillips WJ. Dexmedetomidine for procedural sedation in the emergency department. Eur J Emerg Med. 2010;17:60.